The strong inverse association between plasma concentrations of soluble tumor necrosis factor receptors type 1 with adiponectin/leptin ratio in older women.

Complex inflammatory crosstalk between muscular and adipose organs during ageing is controlled by adipokines and myokines. The Adiponectin/Leptin ratio (A/L ratio) has proven to be a promising biomarker for identifying insulin sensitivity, cardiovascular risk and adipose tissue inflammation. Although the A/L ratio has been related to inflammatory conditions, its ability to associate with or indicate the behavior of other inflammatory mediators remains unknown. The present study aimed to verify the association between the A/L ratio and a panel of inflammatory biomarkers in community-dwelling older women. The plasmatic concentrations of adiponectin, leptin, resistin, brain-derived neurotrophic factor (BDNF), interferon-gamma (IFN-γ), interleukins 2, 4, 5, 6, 8 and 10, tumour necrosis factor (TNF) and its soluble receptors (sTNF-r) 1 and 2 were evaluated in 71 community-dwelling older women with 75 (±7) years. The A/L ratio was negative and inverse correlated with BNDF (r = -0.29; p = 0.01), IL-8 (r = -0.37; p = 0.001) and sTNFr- 1 (r = -0.98; p < 0.001) levels. A strong and inverse association, with proportional effect, between A/L ratio and sTNFr-1 concentrations was found (Adjusted R2 = 0.22; ß = -0.48; p > 0.001). It suggests that the presence of sTNFr-1 causes an inflammatory effect that affect cross-talk between muscle and adipose tissue, contributing to pro-inflammatory imbalance, which may have molecular and functional consequences. In addition, we provide insights into diagnostic biomarkers for inflammation, especially related to muscle wasting and intrinsic capacity in older people.

Assessment of health-related quality of life in patients with Chagas cardiomyopathy using Minnesota living with heart failure questionnaire: A validation study.

OBJECTIVE: Chagas cardiomyopathy (ChC) is the most severe clinical form of Chagas disease and, in association with psychosocial factors, can compromise the health-related quality of life (HRQoL) of affected patients. To date, there is no specific instrument to assess the HRQoL of these patients, and the Minnesota Living with Heart Failure Questionnaire (MLwHFQ), specific for heart failure, is being used both in research and current clinical practice. Therefore, we aimed to verify the validity of the MLwHFQ in the assessment of HRQoL of patients with ChC. METHODS: Fifty patients with ChC (50.6 ± 10.1 years, NYHA I-III) were evaluated. The MLwHFQ, Short-Form of Health Survey (SF-36), Beck Depression Inventory (BDI), and Human Activity Profile (HAP) were applied. All patients underwent echocardiography and Cardiopulmonary Exercise Testing (CPET). RESULTS: The MLwHFQ score correlated with almost all SF-36 domains (with r-value ranging from -0.38 to -0.69), except pain (p = 0.118). The MLwHFQ score also correlated with the BDI score (r = 0.748; p < 0.001), HAP score (r = -0.558; p = 0.001), peak oxygen uptake (r = -0.352; p = 0.01), and left ventricular ejection fraction (r = -0.329; p = 0.021). There was no significant difference in the score found on the MLwHFQ among NYHA classes (p = 0.101), as well as between patients with systolic dysfunction (n = 30) and preserved cardiac function (n = 20) (p = 0.058). Similarly, there was no significant difference in the score found on the physical (p = 0.423) and mental (p = 0.858) components of SF-36 between patients with systolic dysfunction and preserved cardiac function (p = 0.271 and p = 0.609, respectively). There was also no difference in the mental component of SF-36 among NYHA classes (p = 0.673). However, the HRQoL using the physical component of SF-36 was worse in advanced NYHA classes (p = 0.014). CONCLUSION: MLwHF correlated with most SF-36 HRQoL domains, depressive symptoms, physical activity, and systolic function and seems to be valid in assessing the HRQoL of ChC patients.

RELATIONSHIP BETWEEN RESIDUAL DIURESIS AND SARCOPENIA IN PATIENTS ON HEMODIALYSIS.

OBJECTIVE: To assess the association of residual diuresis with sarcopenia in patients with Chronic Kidney Disease (CKD) on hemodialysis. METHODS: Through a cross-sectional study, patients on hemodialysis were subjected to a Dual Energy Radiologic Absorption (DEXA) exam to record muscle mass. Based on the volume of urine collected in 24 hours, patients were classified as anuric (diuresis ≤ 100 mL/day) or non-anuric (diuresis > 100 mL/day). Functional performance was evaluated by Short Physical Performance Battery (SPPB) and muscle strength by handgrip strength and 5-repetition sit-to-stand test. The association between the absence of residual urine and the presence of sarcopenia, low SPPB, and low muscle strength was analyzed using a binary logistic regression model. RESULTS: Ninety-two patients, with a mean age of 54.4 years (95% CI 51.3 - 57.4) and with a mean diuresis volume of 476.3 mL/day (95% CI 320.4 - 632.2) were evaluated (48 anuric and 44 non-anuric). Anuric patients had a 2.77 (95% CI 1.14 - 6.73) times greater probability of sarcopenia and had a 3.55 (1.14 - 11.0) times greater probability of low SPPB, regardless of gender, age, and time on dialysis. Gender was the other associated variable for the presence of sarcopenia, with males having a 3.30 (95% CI 1.34 - 8.13) times higher risk. There were no associations with muscle strength. CONCLUSION: The absence of residual diuresis in patients on hemodialysis is associated with a higher risk of sarcopenia and low functional performance.

Association Between Typologies of Sedentary Behavior and Muscle Strength, Gait Speed, and Balance in Community-Dwelling Older Adults.

Knowledge of how the different types of sedentary behaviors (SB) are associated with functional limitations can guide professionals who work with older adults on better recommendations about the amount of daily time that should be encouraged in each type of SB. The objective was to estimate the associations between two SB typologies (SB television [TV] and SB computer/internet) and the presence of handgrip strength, lower limb strength, gait speed, and balance limitations in Brazilian community-dwelling older adults. This is a cross-sectional study with 1,298 community-dwelling older adults (≥60 years). SB was assessed by self-reporting daily time spent watching TV or using computer/internet (categorized into <2, 3-4, and ≥5 hr/day). Outcomes were handgrip strength, lower limb strength, gait speed, and balance limitations considering referenced cutoff points. Older adults in SB TV ≥5 hr/day had 1.75 (95% confidence interval [CI] [1.07, 2.86]) and 1.88 (95% CI [1.02, 3.46]) times more chances of handgrip strength and gait speed limitations, respectively. On the other hand, those who spent 3-4 and ≥5 hr/day in SB computer/internet had 0.45 (95% CI [0.20, 0.99]) and 0.37 (95% CI [0.15, 0.93]) had less chances of lower limb strength and balance limitations, respectively. In conclusion, functional limitations would be associated differently depending on the type of SB in the older adults sampled.

Environmental opportunities facilitating cognitive development in preschoolers: development of a multicriteria index.

Access to environmental opportunities can favor children's learning and cognitive development. The objectives is to construct an index that synthesizes environmental learning opportunities for preschoolers considering the home environment and verify whether the index can predict preschoolers' cognitive development. A quantitative, cross-sectional, exploratory study was conducted with 51 preschoolers using a multi-attribute utility theory (MAUT). The criteria used for drawing up the index were supported by the literature and subdivided in Group A "Resources from the house" extracted from HOME Inventory including: (1) to have three or more puzzles; (2) have at least ten children's books; (3) be encouraged to learn the alphabet; (4) take the family out at least every 2 weeks. Group B "Screens" (5) caution with using television; (6) total screen time in day/minutes. Group C "Parental Schooling" (7) maternal and paternal education. Pearson correlation analyses and univariate linear regression were performed to verify the relationship between the established index with cognitive test results. The index correlated with the total score of the mini-mental state exam (MMC) and verbal fluency test (VF) in the category of total word production and word production without errors. Multicriteria index explained 18% of the VF (total word production), 19% of the VF (total production of words without errors) and 17% of the MMC. The present multicriteria index has potential application as it synthesizes the preschooler's environmental learning opportunities and predicts domains of child cognitive development.

Association between biomarkers of redox status and cytokines with different patterns of habitual physical activity in eutrophic and overweight/obese preschoolers: multivariate analysis of a cross-sectional study.

BACKGROUND: Although it is well known that obesity is frequently associated with reduced levels of habitual physical activity (HPA), which contributes to determining severe oxidative stress and inflammatory state, this association is however unknown in preschoolers so far. This study aimed to investigate the association between biomarkers of redox status and cytokines with different patterns of HPA according to the adiposity of preschoolers. METHODS: A cross-sectional study was conducted in 50 preschoolers (25 overweight/obese, OW/OB and 25 eutrophic, EU), matched for age, sex, economic level, and maternal education. Total antioxidant capacity (TAC), superoxide dismutase (SOD) and catalase (CAT) activities, substances reactive to thiobarbituric acid (TBARS), soluble tumor necrosis factor receptors (sTNFRs), and leptin levels were evaluated. HPA levels were evaluated by accelerometry (ActiGraph GT9X accelerometer). Correlation, multiple linear regression, and partial least squares regression analysis were used to determine the association between redox status biomarkers and cytokines with different patterns of HPA (HPA level, bouts of moderate to vigorous physical activity [MVPA], and multivariate pattern of HPA) in EU and OW/OB preschoolers. RESULTS: OW/OB preschoolers had lower CAT activity, higher levels of TAC, TBARS, and cytokines, and similar levels of HPA to EU preschoolers. In EU preschoolers, SOD activity exhibited a stronger negative association with moderate intensity ranges of HPA (R2 = 0.18), and negative correlation with sTNFRs (r = -0.40 to -0.46). TBARS had a stronger positive association with ranges of light intensity in the multivariate pattern of HPA (R2 = 0.10). In OW/OB preschoolers, the HPA multivariate associative pattern was predominantly from vigorous intensity ranges. Thus, SOD activity had a positive association with the multivariate pattern of HPA (R2 = 0.38) and MVPA bouts (ß [95% CI] = 0.457 [0.0026. 0.0576]). TAC had a negative association with the multivariate pattern of HPA (R2 = 0.38) and MVPA bouts (ß [95% CI] = -0.718 [-0.0025. -0.0003]). Additionally, leptin levels were lower in OW/OB preschoolers engaged in vigorous physical activity (VPA) (8000-9999 counts/min) for longer periods of time. CONCLUSION: The results of this study indicate that OW/OB preschoolers have higher levels of oxidative stress biomarkers and pro-inflammatory cytokines compared to EU preschoolers. Moreover, VPA may exert antioxidative and anti-inflammatory effects in OW/OB preschoolers.

Prevalence of sarcopenia in older women and level of agreement between the diagnostic instruments proposed by the European Working Group on Sarcopenia in Older People 2 (EWGSOP2).

BACKGROUND: The European Working Group on Sarcopenia in Older People 2 (EWGSOP2) proposed the use of different diagnostic tools to assess sarcopenia. This study aimed to determine prevalence rates of sarcopenia according to the diagnostic instruments proposed by EWGSOP2 and to assess their level of agreement in older Brazilian women. METHODS: A cross-sectional study with 161 community-dwelling older Brazilian women. Probable sarcopenia was assessed through Handgrip Strength (HGS) and the 5-times sit-to-stand test (5XSST). In addition to reduced strength, Appendicular Skeletal Muscle Mass (ASM) (obtained by Dual-energy X-ray absorptiometry) and ASM/height² were considered for diagnosis confirmation. Sarcopenia severity was determined by reduced muscle strength and mass and poor functional performance assessed by Gait Speed (GS), Short Physical Performance Battery (SPPB), and Timed Up and Go test (TUG). McNemar's test and Cochran's Q-test were used to compare sarcopenia prevalence. Cohen's Kappa and Fleiss's Kappa tests were used to assess the level of agreement. RESULTS: The prevalence of probable sarcopenia was significantly different (p < 0.05) when using HGS (12.8%) and 5XSST (40.6%). Regarding confirmed sarcopenia, the prevalence was lower when using ASM/height² than with ASM. Regarding severity, the use of SPPB resulted in a higher prevalence in relation to GS and TUG. CONCLUSION: There were differences in the prevalence rates of sarcopenia and low agreement between the diagnostic instruments proposed by the EWGSOP2. The findings suggest that these issues must be considered in the discussion on the concept and assessment of sarcopenia, which could ultimately help to better identify patients with this disease in different populations.

Diverse mutational spectrum in the 13q14 chromosomal region in a Brazilian cohort of retinoblastoma.

Retinoblastoma is a rare childhood tumor caused by the inactivation of both copies of the RB1 gene. Early diagnosis and identification of heritable RB1 mutation carriers can improve the disease outcome and management via genetic counseling. We used the Multiplex Ligation-dependent Probe Amplification (MLPA) method to analyze the RB1 gene and flanking regions in blood samples from 159 retinoblastoma patients previously negative for RB1 point mutations via Sanger sequencing. We detected a wide spectrum of germline chromosomal alterations, ranging from partial loss or duplication of RB1 to large deletions spanning RB1 and adjacent genes. Mutations were validated via karyotyping, fluorescent in situ hybridization (FISH), SNP-arrays (Single Nucleotide Polymorphism-arrays) and/or quantitative relative real-time PCR. Patients with leukocoria as a presenting symptom showed reduced death rate (p = 0.013) and this sign occurred more frequently among carriers of two breakpoints within RB1 (p = 0.05). All unilateral cases presented both breakpoints outside of RB1 (p = 0.0075). Patients with one breakpoint within RB1 were diagnosed at earlier ages (p = 0.017). Our findings characterize the mutational spectrum of a Brazilian cohort of retinoblastoma patients and point to a possible relationship between the mutation breakpoint location and tumor outcome, contributing to a better prospect of the genotype/phenotype correlation and adding to the wide diversity of germline mutations involving RB1 and adjacent regions in retinoblastoma.

Anti-inflammatory and anti-necrotic effects of lectins from Canavalia ensiformis and Canavalia brasiliensis in experimental acute pancreatitis.

Lectins isolated from Canavalia ensiformis (ConA) and Canavalia brasiliensis (ConBr) are promising molecules to prevent cell death. Acute pancreatitis, characterized by acinar cell necrosis and inflammation, presents significant morbidity and mortality. This study has investigated the effects of ConA and ConBr in experimental acute pancreatitis and pancreatic acinar cell death induced by bile acid. Pancreatitis was induced by retrograde pancreatic ductal injection of 3% sodium taurocholate (Na-TC) in male Swiss mice. ConA or ConBr (0.1, 1 or 10 mg/kg) were intravenously applied to mice 1 h and 12 h after induction. After 24 h, the severity of pancreatitis was evaluated by serum amylase and lipase, histopathological changes and myeloperoxidase assay. Pancreatic acinar cells were incubated with ConA (200 µg/ml) or ConBr (200 µg/ml) and taurolithocholic acid 3-sulfate (TLCS; 500 µM). Necrosis and changes in mitochondrial membrane potential (ΔÑ°m) were detected by fluorescence confocal microscopy. Treatment (post-insult) with ConA and ConBr decreased pancreatic damage caused by retrograde injection of Na-TC in mice, reducing pancreatic neutrophil infiltration, edema and necrosis. In addition, ConA and ConBr decreased pancreatic acinar cell necrosis and depolarization of ΔÑ°m caused by TLCS. The inhibition of necrosis was prevented by the lectin domain blockade. In conclusion, ConA and ConBr markedly inhibited in vitro and in vivo damage, effects partly dependent on the interaction with mannose residues on acinar cells. These data support the potential application of these proteins for treatment of acute pancreatitis.

Determining factors of functioning in hemodialysis patients using the international classification of functioning, disability and health.

BACKGROUND: Hemodialysis (HD) treatment affects functioning, physical activity level, clinical biomarkers, and body composition. However, the association between these variables with functioning, considering International Classification of Functioning, Disability and Health (ICF) domains remains unclear. Thus, the aim of this study was to investigate the possible association between physical activity, biomarkers, and body composition with functioning in HD patients in reference to the ICF. METHODS: Eighty HD patients performed different tests grouped according to ICF domain: Body structure and function - handgrip strength (HS), 5-repetition sit-to-stand test, and 60-s sit-to-stand test (5-STS, 60-STS, respectively); Activity - short physical performance battery (SPPB); and Participation - participation scale questionnaire. Physical activity [Human Activity Profile questionnaire (HAP)], body composition (Dual-energy X-ray absorptiometry), Parathormone (PTH), and alkaline phosphatase were analyzed as possible variables associated with ICF domains. Data analyses were performed using simple and multiple regression models adjusted for age, duration of HD, and diuresis volume. RESULTS: In the body structure and function domain, appendicular lean mass, PTH level, and age were associated with HS (R2 = 0.558); HAP and PTH were associated with 5-STS (R2 = 0.263); and HAP, PTH, duration of HD, and age were associated with 60-STS (R2 = 0.337). In the activity domain, HAP, PTH, alkaline phosphatase, duration of HD, age, and body fat were associated with SPPB (R2 = 0.689). Finally, only HAP was associated with the participation scale (R2 = 0.067). CONCLUSION: Physical activity and PTH levels are determinant protagonists of functioning in all ICF domains in hemodialysis patients.

Physical environmental opportunities for active play and physical activity level in preschoolers: a multicriteria analysis.

BACKGROUND: Active play opportunities seems to influence the level of physical activity during childhood. However, a gap remains about which environmental opportunities including the daycare physical environment could have a positive impact on the level of physical activity in preschoolers. OBJECTIVES: (1) To develop an index to measure the environmental opportunities of free active play for preschoolers of middle-income countries; (2) to check the relationship and contribution of the index to explain objectively the level of physical activity. METHODS: A quantitative, cross-sectional, exploratory study with 51 preschool children. The established criteria for the index according to the literature were: (1) Outdoor time on typical days of the week. (2) Outdoor time on a typical weekend day. (3) The presence of internal space and external environment in the child's home that allows playing. (4) Presence of patio with space for games at the school. (5) Presence of a playground with a toy at the school. We applied multi-attribute utility theory for the determination of the multicriteria index of physical environmental opportunities. Pearson's correlation analysis and simple linear regression were used to verify the association between the index and the physical activity level. RESULTS: The index showed a positive correlation with the level of physical activity, e.g., the average time of MVPA (r = 0.408, p = 0.003). The univariate linear regression demonstrated that the quality of physical environmental opportunities for physical activity explained 20% of the preschooler's classification as active and 16% of the time in moderate to vigorous physical activity (p < 0.001). CONCLUSION: Physical environmental opportunities for active play have a positive effect on physical activity in preschoolers and should be encouraged in different social segments.

Association between executive functions and gross motor skills in overweight/obese and eutrophic preschoolers: cross-sectional study.

BACKGROUND: Preschool age (3-5 years old) is a crucial period for children to acquire gross motor skills and develop executive functions (EFs). However, the association between the qualitative gross motor skills and EFs remains unknown in preschoolers, especially among overweight and obese children. METHODS: This was a cross-sectional, exploratory, and quantitative study carried out on 49 preschool children, divided into two subgroups according to their body mass index (overweight/obese: 24; eutrophic [normal weight]: 25). The mean age was 4.59 years. More than half of the sample were boys (55%) and most of the mothers had completed high school (67%) and were class C socioeconomic level (63%). Gross motor skills were assessed using the Test of Gross Motor Development-2, while EFs were evaluated using Semantic verbal fluency (SVF), Tower of Hanoi (TH), Day/Night Stroop, and Delayed Gratification tests. Multiple linear regression models adjusted for sex, age, maternal education, socioeconomic status, quality of the home environment, and quality of the school environment using the stepwise method were executed, considering the cognitive tasks as independent variables and gross motor skills as dependent variable. RESULTS: The overweight/obese preschoolers showed worse locomotor skills than their eutrophic peers and below average gross motor quotient (GMQ). Overweight/obese girls performed worse in OC skills than boys with excess weight. SVF (number of errors) and TH (rule breaks) explained 57.8% of the variance in object control (OC) skills and 40.5% of the variance in GMQ (p < .05) in the overweight/obese children. Surprisingly, there was no significant association between any of the EF tasks and gross motor skills in the eutrophic children. CONCLUSION: A relationship between EF tasks (number of errors in SVF and rule breaks in TH) and gross motor skills (OC and GMQ) was demonstrated in the overweight/obese preschoolers, indicating that worse cognitive flexibility, working memory, planning, and problem solving are associated with worse gross motor skills in this population when compared to eutrophic children.

How much time in sedentary behavior is associated with probable sarcopenia in older adults?

Sedentary activities, such as watching television and using the computer, are frequent conditions in older adults and can be associated with sarcopenia. The objectives of this study were: (a) to establish sedentary behavior (SB) cutoff values for screening probable sarcopenia in community-dwelling older adults and (b) to verify the association between SB and probable sarcopenia according to the established cutoff point. This was a cross-sectional study including 1,165 community residents in Florianopolis/SC. SB was assessed using the International Physical Activity Questionnaire. The outcome was probable sarcopenia (assessed by time ≥ 15 s in the Five times sit-to-stand test). The cut-off points found for SB were time > 120 min/day [AUC: 0.54 (95%CI: 0.51; 0.57)] watching TV or video/DVD and ≤ 20 min/day [AUC: 0.59 (95%CI: 0.56;0.62)] using computer/internet. Older adults with SB had 1.30 (95% CI: 1.01; 1.66) and 1.46 (95% CI: 1.08; 1.96) greater chances of having sarcopenia, respectively.

Reliability and validity of specific quality of life assessment questionnaires related to chronic venous insufficiency: a systematic review.

This systematic review aimed to discuss the main findings regarding the reliability and validity of health-related quality of life questionnaires for chronic venous insufficiency. Searches were performed on the MEDLINE, CINAHL, Web of Science, LILACS, and Scopus databases. The search terms used were related to "venous insufficiency", and "quality of life". The CIVIQ-20 and CIVIQ-14 instruments had adequate internal consistency and both were able to discriminate disease severity. The VEINES-QoL showed adequate internal consistency but was not able to discriminate disease severity. Most studies did not demonstrate a correlation between VEINES-QoL and the mental component of the SF-36. The AVVQ had inadequate reliability but its validity was also doubtful when compared to the SF-36. The VARIShort demonstrated good internal consistency, reproducibility, and validity, but only the original study was included. For venous leg ulcers, the CCVUQ showed adequate reliability and validity when compared to VLU-QoL.

Esta revisão sistemática objetivou discutir os principais achados sobre a confiabilidade e validade dos questionários de qualidade de vida relacionada à saúde na insuficiência venosa crônica. A busca foi realizada nas bases de dados MEDLINE, CINAHL, Web of Science, LILACS e Scopus. Os termos de busca foram relacionados a "insuficiência venosa" e "qualidade de vida". O Chronic Lower Limb Venous Insufficiency Questionnaire (CIVIQ)-20 e o CIVIQ-14 apresentaram consistência interna adequada e foram capazes de discriminar a gravidade da doença. O Venous Insufficiency Epidemiological and Economic Study ­ Quality of Life (VEINES-QoL) apresentou consistência interna adequada, mas não foi capaz de discriminar a gravidade da doença. A maioria dos estudos não demonstrou associação do VEINES-QoL com o componente mental do Short Form Health Survey (SF-36). O Aberdeen Varicose Vein Questionnaire (AVVQ) apresentou confiabilidade inadequada e validade duvidosa quando comparado ao SF-36. O VARIShort demonstrou consistência interna, reprodutibilidade e validade boas, mas apenas o estudo original foi incluído. Na úlcera venosa, o Charing Cross Venous Ulcer Questionnaire (CCVUQ) apresentou confiabilidade e validade adequadas quando comparado ao Venous Leg Ulcer Quality of Life (VLU-QoL).

Molecular alterations in retinoblastoma beyond RB1.

Retinoblastoma is the most common malignant ocular tumor in children. Although RB1 alterations are most frequently involved in the etiology of retinoblastoma, candidate driver events and somatic alterations leading to cell transformation, tumor onset and progression remain poorly understood. In this study, we identified novel genomic alterations in tumors with a panel of 160 genes. Sanger sequencing and Multiplex Ligation-dependent Probe Amplification (MLPA) were initially performed for identifying patients without apparent RB1 alterations in blood DNA. Subsequently, NGS analyses of 24 paired (blood/tumor) samples of these patients were carried out for identifying somatic mutations and copy number variation in RB1 and other 159 genes. One novel pathogenic RB1 mutation and seven novel VUS were identified as well as 90 novel pathogenic mutations in 61 other genes. Twenty-three genes appeared exclusively mutated in tumors without altered RB1 alleles and three frequently affected biological pathways while five other tumors did not show pathogenic RB1 alterations or SNV/indels in 159 other genes. Curiously, deletion of GATA2, AKT1, ARID1A, DNMT3A, MAP2K2, MEN1, MTOR, PTCH1 and SUFU (in homo- or heterozygosity) were exclusively found in these tumors when compared to those with any pathogenic alterations, probably indicating genes that might be essential for the development of retinoblastoma regardless of a functional RB1. Identification of genes associated with retinoblastoma will contribute to understanding presently unknown aspects of this malignancy, which might be essential for its initiation and progression, as well as providing valuable molecular markers.

Miconia albicans and Curcuma longa herbal medicines positively modulate joint pain, function and inflammation in patients with osteoarthritis: a clinical study.

This study aims to evaluate the analgesic and modulating effect of Curcuma longa and Miconia albicans herbal medicines in knee's osteoarthritis (OA) treatment. This longitudinal study evaluated 24 patients with OA. The patients were divided into three groups: ibuprofen (1200 mg/day), C. longa (1000 mg/day) and M. albicans (1000 mg/day). The medications were applied orally for 30 days. The synovial fluid of the knee joint was collect at the first (day 0) and the last medical (day 30) consultation. The groups treated with herbal medicines presented the same results when compared to Ibuprofen. The comparison of the means of Total WOMAC for M. albicans before and after treatment presented a statistically significant difference (mean day 0 = 57.19; mean day 30 = 31.02) as well as variation of Total WOMAC for C. longa (mean day 0 = 54.79; mean day 30 = 37.08). The WOMAC Total and the VASP were compared, it was found that there was a significant decrease in the means in the C. longa and M. albicans groups, as well as in the Ibuprofen group after treatment. The study demonstrated that the treatment of knee OA with C. longa or M. albicans positively interferes with patients pain and functionality, decreased WOMAC and VASP scores, leading to functional improvement of these patients. This is the first clinical study demonstrating the analgesic and anti-inflammatory effect on knee osteoarthritis from M. albicans comparable to Ibuprofen drug.

An update on potential links between type 2 diabetes mellitus and Alzheimer's disease.

Alzheimer's disease (AD) and type 2 diabetes (T2D) major feature is insulin resistance. Brain and peripheral insulin resistance lead to hyperglycemia, which contributes to the development of T2D-linked comorbidities, such as obesity and dyslipidemia. Individuals with hyperglycemia in AD present with neuronal loss, formation of plaques and tangles and reduced neurogenesis. Inflammation seems to play an essential role in the development of insulin resistance in AD and T2D. We conducted a literature review about the links between AD and T2D. Alterations in glucose metabolism result from changes in the expression of the insulin receptor substrates 1 and 2 (IRS-1 and IRS-2), and seem to be mediated by several inflammatory pathways being present in both pathologies. Although there are some similarities in the insulin resistance of AD and T2D, brain and peripheral insulin resistance also have their discrete features. Failure to activate IRS-1 is the hallmark of AD, while inhibition of IRS-2 is the main feature in T2D. Inflammation mediates the alterations in glucose metabolism in AD and T2D. Targeting inflammation and insulin receptors may be a successful strategy to prevent and ameliorate T2D and AD symptoms.

Decreased percentage of CD4+ lymphocytes expressing chemokine receptors in bipolar disorder.

OBJECTIVE: Although accumulating evidence supports the hypothesis that immune/inflammatory mechanisms are associated with the pathophysiology of bipolar disorder (BD), data about the profile of chemokines (chemotactic cytokines) and chemokine receptors are still scarce. The current study was designed to evaluate the expression of chemokine receptors on lymphocytes of patients with BD in comparison with controls. METHODS: Thirty-three patients with type I BD (N = 21 in euthymia; N = 6 in mania/hypomania; N = 6 in depression) and 22 age- and sex-matched controls were subjected to clinical evaluation and peripheral blood draw. The expression of chemokine receptors CCR3, CCR5, CXCR4, and CXCR3 on CD4+ and CD8+ lymphocytes was assessed by flow cytometry. RESULTS: Patients with BD had decreased percentage of CD4+CXCR3+ (p = 0.024), CD4+CCR3+ (p = 0.042), and CD4+CCR5+ (0.013) lymphocytes in comparison with controls. The percentage of both CD4+ and CD8+ lymphocytes expressing the chemokine receptor CXCR4 was similar in patients with BD and controls. Likewise, the percentages of CD8+CXCR3+, CD8+CCR3+, and CD8+CCR5+ lymphocytes were similar in patients with BD and controls. CONCLUSION: Our findings reinforce the hypothesis that immune pathways, especially involving CD4+ lymphocytes, are involved in the physiopathology of BD.

Central cholinergic activation induces greater thermoregulatory and cardiovascular responses in spontaneously hypertensive than in normotensive rats.

There is evidence that central cholinergic stimulation increases heat dissipation in normotensive rats besides causing changes on the cardiovascular system via modulation of baroreceptors activity. However, the contribution of the central cholinergic system on thermoregulatory responses and its relationship with cardiovascular adjustments in spontaneously hypertensive rats (SHRs), an animal model of reduced baroreceptor sensitivity and thermoregulatory deficit, has not been completely clarified. Therefore, the aim of this study was to verify the involvement of the central cholinergic system in cardiovascular and thermoregulatory adjustments in SHRs. Male Wistar rats (n = 17) and SHRs (n = 17) were implanted with an intracerebroventricular cannula for injections of 2 µL of physostigmine (phy) or saline solution. Tail temperature (Ttail), internal body temperature (Tint), systolic arterial pressure (SAP), heart rate (HR) and metabolic rate were registered during 60 min while the animals remained at rest after randomly receiving the injections. The variability of the SAP and the HR was estimated by the fast Fourier transform. Phy treatment began a succession of cardiovascular and thermoregulatory responses that resulted in increased SAP, reduced HR and increased Ttail in both Wistar and SHRs groups. The magnitude of these effects seems to be more intense in SHRs, since the improvement of heat dissipation reflected in Tint. Taken together, these results provide evidence that hypertensive rats present greater cardiovascular and thermoregulatory responses than normotensive rats after central cholinergic stimulation.

Physiological, cellular and biochemical thermal stress response of intertidal shrimps with different vertical distributions: Palaemon elegans and Palaemon serratus.

The ability to cope with high temperature variations is a critical factor in intertidal communities. Two species of intertidal rocky shore shrimps (Palaemon sp.) with different vertical distributions were collected from the Portuguese coast in order to test if they were differentially sensitive to thermal stress. Three distinct levels of biological organization (organismal, biochemical, and cellular) were surveyed. The shrimp were exposed to a constant rate of temperature increase of 1°C x h(-1), starting at 20°C until reaching the CTMax (critical thermal maximum). During heat stress, two biomarkers of protein damage were quantified in the muscle via enzyme-linked immunosorbent assays: heat shock proteins HSP70 (hsp70/hsc70) and total ubiquitin. Muscle histopathological alterations caused by temperature were also evaluated. CTMax values were not significantly different between the congeners (P. elegans 33.4 ± 0.5 °C; P. serratus 33.0 ± 0.5 °C). Biomarker levels did not increase along the temperature trial, but P. elegans (higher intertidal) showed higher amounts of HSP70 and total ubiquitin than P. serratus (lower intertidal). HSP70 and total ubiquitin levels showed a positive significant correlation in both species, suggesting that their association is important in thermal tolerance. Histopathological observations of muscle tissue in P. serratus showed no gross alterations due to temperature but did show localized atrophy of muscle fibers at CTMax. In P. elegans, alterations occurred at a larger scale, showing multiple foci of atrophic muscular fascicles caused by necrotic or autolytic processes. In conclusion, Palaemon congeners displayed different responses to stress at a cellular level, with P. elegans having greater biomarker levels and histopathological alterations.